A novel porous hydroxyapatite scaffold (pHAMG) enhances angiogenesis and osteogenesis around dental implants by regulating the immune microenvironment.

OBJECTIVE: The purpose was to evaluate whether a novel porous hydroxyapatite (HA) scaffold with a 25-30-µm groove structure (pHAMG) may improve bone osteogenesis, angiogenesis, and bone integration of titanium dental implants in animal models. METHODS: The pHAMG was prepared by chemical precipitation method and its elemental composition and crystal structure were evaluated. The ability of the scaffolds to induce ectopic osteogenesis and the ability of scaffolds combined with titanium dental implants to induce orthotopic peri-implant angiogenesis, osteogenesis, and osteointegration were tested after implantation into the femur muscle pocket in rats and the mandibular defects in beagle dogs, respectively. The elemental composition was evaluated by SEM-EDS; the expression of the relevant osteogenic/inflammation marker and the anti-/pro-inflammation markers was evaluated by immunostaining and immunofluorescence, respectively. RESULTS: In animal experiments with ectopic and peri-implant osteogenesis, pHAMG resulted in significantly larger neovascularization by hematoxylin-eosin staining, as well as deposition of collagen fibers by Masson staining than HA. Meanwhile, microgrooves in pHAMG upregulate more bone morphogenetic protein (BMP) 2 and interleukin-4 (IL-4) and -10 (IL-10) and downregulate more IL-1ß and tumor necrosis factor-α (TNF-α) than that in HA. The pHAMG showed greater expression of arginase (Arg)-1 and lower expression of inducible nitric oxide synthase (iNOS) than HA. CONCLUSION: The novel pHAMG can better repair bone defects in ectopic and orthotopic model. It also transfers macrophages to anti-inflammatory phenotypes, promoting angiogenic and osteogenesis in scaffolds, and bone integration in implants. CLINICAL RELEVANCE: The novel pHAMG induce greater osteogenesis and angiogenesis which could be utilized in the clinical treatment.

The immunologic status of newborns born to SARS-CoV-2-infected mothers in Wuhan, China.

BACKGROUND: Immunologic dysfunction due to coronavirus disease 2019 (COVID-19) is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells. OBJECTIVE: We sought to analyze the immune status of newborns from mothers with COVID-19 in the third trimester. METHODS: Along with collecting the clinical data from 51 newborns and their respective mothers, we recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns. RESULTS: None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of severe acute respiratory syndrome coronavirus 2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, whereas IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period. CONCLUSIONS: COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.

High-dose of intravenous immunoglobulin modulates immune tolerance in premature infants.

BACKGROUND: Intravenous immunoglobulin (IVIG) is commonly used to improve the immunomodulatory effects, although its regulatory effect on premature Treg cells is unclear. The purpose of this study is to study the effect of high dose of IVIG (HD-IVIG) on Treg cells expression and cytokine profile in premature birth. METHODS: Fifty-two premature infants were enrolled in this study and thirty-one premature infants who were suspected to have intrauterine infection received HD-IVIG (1-2 g/kg) at the first day of birth; the remaining 21 premature infants were assigned as the control group. The peripheral blood CD4 + T and foxp3+ Treg cells were checked by flow cytometry, and cytokine concentrations were detected by cytometric bead array. RESULTS: With the gestational age growth, peripheral blood CD4 + T and foxp3+ Treg cells of prematurity gradually declined from 50% to 35% and from 8% to 6%, respectively. Meanwhile, HD-IVIG increased the percentage of CD4 + T and foxp3+ Treg cells compared with their baseline levels (p < 0.001). HD-IVIG demonstrated different regulating effects on cytokines secretion, increased IL-17 and TGF-ß, and inhibited IL-6 secretion. CONCLUSION: Our results demonstrated that HD-IVIG not only enhanced the premature immune tolerance, but also suppressed the excessive inflammation response mediated by IL-6. TRIAL REGISTRATION: This study was under the clinical study registration (ChiCTR-ORC-16008872, date of registration, 2016-07-21).

Respiratory syncytial virus NS1 protein degrades STAT2 by inducing SOCS1 expression.

OBJECTIVES: Respiratory syncytial virus (RSV) nonstructural protein NS1 (NS1) has been shown to block interferon (IFN)-inducible antiviral signaling. The suppressor of cytokine signaling (SOCS) gene family could utilize a feedback loop to block the activation of the JAK/STAT signaling pathway, further inhibiting the activation of host type I IFN. We evaluated the role of the SOCS1 and SOCS3 genes in this antiviral mechanism. MATERIAL AND METHODS: A humanized stable NS1 (rich in GC)-expressing plasmid was constructed, and A549 cells were transfected with it. Expression of the SOCS1, SOCS3, RIG-I, and TLR3 mRNAs was measured with real-time PCR. STAT2 and pSTAT2 expression was determined with Western blotting. RESULTS: RSV NS1 upregulated SOCS1 mRNA expression 30-fold increase compared with the baseline level in very early phase (p < 0.01), and silence of RIG-I or TLR3 mRNA did not affect NS1-induced SOCS1 expression. NS1 inhibited IFN-α-induced STAT2 phosphorylation and degraded STAT2 in a time-dependent manner compared with the empty-vector control (p < 0.05). CONCLUSION: RSV NS1 upregulates SOCS1 expression in a RIG-I- and TLR3-independent pathway, to inhibit STAT2 phosphorylation.

Primary amebic meningoencephalitis in children: A case report and literature review.

This article presents the diagnostic and therapeutic journey of a 14-year-old male patient diagnosed with Primary Amebic Meningoencephalitis (PAM), incorporates a review of pertinent literature and a discussion on recent advancements in the study of this condition. The patient presented with symptoms of fever and headache for three days, accompanied by seizures and a half-day episode of altered consciousness. Upon admission, clinical findings included a mild coma, respiratory distress, rigidity of limbs, and negative pathological reflexes. The patient's history showed in a local outdoor pond swimming in July and August of the same year. Metagenomic Next-Generation Sequencing (mNGS) of the cerebrospinal fluid identified the presence of Naegleria fowleri. Cranial CT and MRI scans indicated signs of brain edema and meningitis. The patient was confirmed with pediatric primary amebic meningoencephalitis. A 45-day comprehensive treatment regimen was administered, encompassing anti-amebic medications, anticonvulsant therapy, management of brain edema, and intracranial pressure reduction. This case represents the longest survival period recorded for such pediatric cases in China. The purpose of this report is to heighten clinical awareness of PAM, share diagnostic and therapeutic insights, expand upon existing treatment approaches, and ultimately contribute to improving the survival rates of PAM patients.

Predominance of A2063G mutant strains in the Mycoplasma pneumoniae epidemic in children: A clinical and epidemiological study in 2023 in Wuhan, China.

OBJECTIVES: The prevalence of respiratory infectious diseases has changed in the post-COVID-19 epidemic era, and mycoplasma pneumoniae (MP) infection in children has attracted wide attention. METHODS: Children hospitalized for pneumonia in Wuhan, China, in 2023 were enrolled. Respiratory secretions were obtained for the targeted next-generation sequencing (tNGS) including mutation of MP. Pulmonary inflammation was divided into bronchopneumonia and pulmonary consolidation/atelectasis according to lung computed tomography imaging. RESULTS: Of the 667 pediatric pneumonia, 478 were MP positive (72%). The positive rate of MP detected by tNGS increased from April, and MP had become the primary pathogen of pneumonia in children in 2023. The 23S rRNA mutations were all A2063G, accounting for 85% of detected MP. The clinical symptoms of the mutant and wild-type strains were similar, with half of them experiencing atelectasis and lung consolidation. Early bronchoscopic lavage combined with azithromycin in pediatric pulmonary consolidation was an effective therapy strategy, which could be an alternative selection to MP pneumonia treatment. CONCLUSIONS: A2063G mutant strain MP was the primary pathogen of mycoplasma pneumoniae in children recently, which was often complicated by extra-pulmonary symptoms and complications.

Store-operated Ca2+ entry is involved in transforming growth factor-ß1 facilitated proliferation of rat airway smooth muscle cells.

OBJECTIVE: To investigate the role and underlying mechanisms of store-operated Ca(2+) entry (SOCE) in mediating the promoting effect of transforming growth factor (TGF)-ß1 on the proliferation of airway smooth muscle cells (ASMCs). METHODS: Rat bronchial smooth muscle cells were cultured as we described previously. The intracellular Ca(2+) concentration ([Ca(2+)]i) of ASMCs was measured by laser confocal microscope Ca(2+) fluorescence imaging with Fluo-3/AM. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and p27 expression assay were used to determine the proliferation rate of ASMCs. RESULTS: We demonstrated that TGF-ß1 (10 ng/ml) increased basal (Ca(2+)]i) level, [Ca(2+)]i rise induced by thapsigargin-induced Ca(2+) release and SOCE in rat ASMCs. This effect of TGF-ß1 on SOCE was not inhibited by glucocorticoid dexamethasone (DXM, 100 nM), antioxidant α-tocopherol (100 µM), and intermediate-conductance Ca(2+)-activated K(+) channels (IKCa) inhibitor charybdotoxin (100 nM), suggesting that reactive oxygen species and IKCa channels might not mediate the effect of TGF-ß1. TGF-ß1 slightly increased the expression of Orai1 and STIM1, two important molecules involved in the molecule component and regulation of SOC channels, in the presence of 10% fetal bovine serum (FBS). The proliferation of ASMC stimulated with 2.5% FBS was promoted by TGF-ß1, and partly inhibited by non-specific Ca(2+) channel blocker SKF-96365 (10 µM) and Ni(2+) (100 µM). DXM, α-tocopherol, and charybdotoxin had no effect on the proliferation promoted by TGF-ß1. CONCLUSION: TGF-ß1 promotes ASMC proliferation partly through increasing the expression and activity of SOC channels.

Role of protein kinase C in the activation of store-operated Ca(2+) entry in airway smooth muscle cells.

Store-operated Ca(2+) channels (SOCs) are plasma membrane Ca(2+) permeable channels activated by depletion of intracellular Ca(2+) store. Ca(2+) entry through SOCs is known as store-operated Ca(2+) entry (SOCE), which plays an important role in the functional regulation of airway smooth muscle cells (ASMCs). Protein kinase C (PKC) has been shown to have an activating or inhibiting effect on SOCE, depending on cell types and PKC isoforms that are involved. In ASMCs, the effect of PKC on SOCE has not been elucidated so far. In this study, the role of PKC in the activation of SOCE in rat ASMCs was examined by using Ca(2+) fluorescence imaging technique. The results showed that acute application of PKC activators PMA and PDBu did not affect SOCE induced by the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin. The non-selective PKC inhibitor chelerythrine significantly inhibited thapsigargin- and bradykinin-induced SOCE. RT-PCR assay identified PKCα, δ and ɛ isoforms in rat ASMCs. PKCα-selective inhibitor Gö6976 and PKCɛ-inhibiting peptide Epsilon-V1-2 had no effect on SOCE; by contrast, PKCδ-selective inhibitor rottlerin attenuated SOCE dramatically, suggesting that PKCδ was the major PKC isoform involved in the activation of SOCE in ASMCs. Moreover, PKC down-regulation by extended exposure to high doses of PMA or PDBu also reduced SOCE, confirming the essential role of PKC in the activation of SOCE in ASMCs. In addition, PKC down-regulation did not influence the expression of stromal interaction molecule 1 (STIM1) and Orai1, two elementary molecules in the regulation and activation of SOCs. These results identified PKCδ as an essential PKC isoform involved in the activation of SOCE, and confirmed that PKC regulates the function of ASMCs in a SOCE-dependent manner.

Human Parvovirus B19 Nonstructural Protein 1 Regulates GATA1 Expression via the Notch Signaling Pathway in K562 Cell Line.

BACKGROUND: Human parvovirus B19 (B19) infection can affect the hematopoietic arrest in fetus by hindering the differentiation and maturation of erythroid progenitor cells. B19 nonstructural protein 1 (NS1) has been shown to inhibit the differentiation of erythroid progenitor cells. The goal of this study is to explore the role of B19 NS1 in the regulation of GATA1 and Notch signaling pathway in hematopoietic cells. METHODS: The B19 NS1 expression plasmid was reconstituted, and the possibility of NS1 regulating GATA1 and GATA2 expression modulated by Notch-Hes pathway was tested by qRT-PCR and western blot. Immunofluorescence assays were conducted to visualize pNS1 in K562 cells. RESULTS: We demonstrate that B19 NS1 inhibited GATA1 and induced Hes1/Hes5, which is involved in the activation of Notch signaling pathway. Meanwhile, NS1 exhibited promoting effects on GATA2 expression. Activation of the Notch signaling pathway up-regulated its downstream transcriptional repressor family Hes, thereby inhibiting the expression of GATA gene in K562 cells. CONCLUSIONS: The results show that B19 NS1 protein negatively regulates GATA1 related nuclear transcription and may interfere with hematopoietic cell differentiation.

Alveolar macrophages and airway hyperresponsiveness associated with respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a ubiquitous pathogen of viral bronchiolitis and pneumonia in children younger than 2 years of age, which is closely associated with recurrent wheezing and airway hyperresponsiveness (AHR). Alveolar macrophages (AMs) located on the surface of the alveoli cavity are the important innate immune barrier in the respiratory tract. AMs are recognized as recruited airspace macrophages (RecAMs) and resident airspace macrophages (RAMs) based on their origins and roaming traits. AMs are polarized in the case of RSV infection, forming two macrophage phenotypes termed as M1-like and M2-like macrophages. Both M1 macrophages and M2 macrophages are involved in the modulation of inflammatory responses, among which M1 macrophages are capable of pro-inflammatory responses and M2 macrophages are capable of anti-proinflammatory responses and repair damaged tissues in the acute and convalescent phases of RSV infection. Polarized AMs affect disease progression through the alteration of immune cell surface phenotypes as well as participate in the regulation of T lymphocyte differentiation and the type of inflammatory response, which are closely associated with long-term AHR. In recent years, some progress have been made in the regulatory mechanism of AM polarization caused by RSV infection, which participates in acute respiratory inflammatory response and mediating AHR in infants. Here we summarized the role of RSV-infection-mediated AM polarization associated with AHR in infants.

Respiratory Syncytial Virus Nonstructural Protein 1 Promotes 5-Lipoxygenase via miR-19a-3p.

Background: Respiratory syncytial virus (RSV) infection can regulate the expression of a wide range of noncoding microRNAs (miRNAs), in which mir-19a-3p can participate in airway inflammatory response by regulating 5-lipoxygenase (5-LO) pathway. RSV nonstructural protein (NS) 1 is involved in the airway hyperresponsiveness during RSV infection. Methods: The expression levels of miR-19a-3p and inflammatory signaling-related indicators were detected using quantitative real-time PCR and western blot analyses on the A549 cells transfected with NS1 expression plasmids (pNS1). The 5-LO-mediated inflammatory signaling pathway was assessed when the miR-19a-3p or 5-LO was inhibited. Results: The immunofluorescence analysis showed that the plasmid-mediated NS1 protein was observed in both the cytoplasm and nucleus. The expression level of miR-19a-3p was significantly upregulated in the pNS1 or RSV-treated cells, which was reversed by the NS1 small interfering RNA. In addition, pNS1 also upregulated the expression of 5-LO, interleukin-5 (IL-5), and leukotriene B4 (LTB4), which was also significantly inhibited by the miR-19a-3p antagonists. The 5-LO inhibitor MK886 prevented the increase in the expression level of IL-5 induced by pNS1. Conclusions: These results suggested that the RSV NS1 might play an important role in the pathogenesis of RSV by activating the 5-LO and subsequent inflammatory cytokines through miR-19a-3p.

Comparison of short-term efficacy of MIS-TLIF and Endo-LIF in the treatment of single-segment degenerative lumbar diseases.

Background: A prospective controlled study was conducted to compare the short-term clinical results and postoperative complications of minimally invasive transforaminal lumbar decompression and fusion (minimally invasive surgery transforaminal lumbar interbody fusion, MIS-TLIF) and percutaneous endoscope-assisted transforaminal lumbar interbody fusion (endoscopic lumbar interbody fusion, Endo-LIF) in the treatment of single-segment degenerative lumbar diseases, to provide some scientific guidance for clinicians to select surgical treatment for patients with lumbar degeneration. Methods: From October 2020 to October 2021, a total of 62 patients were enrolled, with 31 patients in the MIS-TLIF group and 31 patients in the Endo-LIF group. All patients were followed up for 6 months. The following information from the two groups of patients was recorded: (1) operation time, radiation exposure time, intraoperative blood loss, bed rest time, and hospital stay; (2) ODI score (The Oswestry Disability Index), low back pain VAS score (Visual Analogue Scale), and lumbar vertebra JOA score (Japanese Orthopaedic Association Scores) 1 day before the operation; 1, 3, 6 days after operation; and 1, 3 and 6 months after operation. (3) X-ray evaluations of lumbar fusion at the last follow-up. Results: There were significant differences in operation time, intraoperative fluoroscopy time, and hospitalization cost between the two groups. The MIS-TLIF group was significantly better than the Endo-LIF group, and the intraoperative bleeding volume of the Endo-LIF group was significantly better than that of the MIS-TLIF group, but there was no significant difference in postoperative bed rest time and postoperative hospital stay. There was no significant difference in the scores of ODI, VAS, and JOA between the two groups before and after the operation. At the last follow-up, the fusion rate was 100% in the MIS-TLIF group and 100% in the Endo-LIF group. Conclusions: There was no significant difference in short-term clinical efficacy and safety between Endo-LIF and MIS-TLIF in the treatment of single-segment degenerative lumbar diseases, but MIS-TLIF was significantly better than Endo-LIF in terms of the operation time, hospitalization cost, and fluoroscopy time, and Endo-LIF was significantly better than MIS-TLIF in terms of intraoperative blood loss.

Diagnostic values of 2 different techniques for controversial lumbar disc herniation by conventional imaging examination: 3D-DESS vs. CT plain scan.

Background: The aim of this study was to explore the significance of three-dimensional double-echo steady-state (3D-DESS) sequence and multidetector computed tomography (CT) plain scan in the diagnosis of lumbar disc herniation (LDH) remaining controversial in conventional magnetic resonance imaging (MRI), and to compare the efficiency between 3D-DESS and CT in diagnosing controversial patients by conventional MRI. Methods: A total of 61 patients with controversial LDH diagnosed by conventional MRI were collected. Before operation, the disease of these patients was further confirmed by 3D-DESS sequences and continuous CT plain scan from L3 to S1. Finally, for patients whose postoperative curative effect was marked and symptoms were obviously alleviated, the sensitivity, specificity and accuracy. Results: Among, 59 patients with remarkably relieved symptoms after operation were included, and 2 patients with varying degrees of non-remission of pain and partial dysfunction after operation were excluded. The sensitivity, specificity and accuracy of 3D-DESS were 94.6, 100 and 94.9%, respectively, and those of CT were 75.0, 33.3 and 72.9%, respectively. Conclusion: 3D-DESS is a very useful diagnostic method for patients with some special types of LDH that remain controversial in conventional imaging diagnostic methods. Through 3D-DESS, the morphology of lumbosacral nerve roots can be directly observed, which is conducive to the improvement of the sensitivity, specificity and accuracy, thus further reducing the misdiagnosis rate. Moreover, 3D-DESS plays a guiding role in the formulation of operative methods.

Metabolomics Characterize the Differential Metabolic Markers between Bama Xiang Pig and Debao Pig to Identify Pork.

The Bama Xiang pig (BM) is a unique pig species in Guangxi Province, China. Compared to other breeds of domestic pig, such as the Debao pig (DB), it is smaller in size, better in meat quality, resistant to rough feeding and strong in stress resistance. These unique advantages of Bama Xiang pigs make them of great edible value and scientific research value. However, the differences in muscle metabolites between Bama Xiang pigs (BM) and Debao pigs (DB) are largely unexplored. Here, we identified 214 differential metabolites between these two pig breeds by LC-MS. Forty-one such metabolites are enriched into metabolic pathways, and these metabolites correspond to 11 metabolic pathways with significant differences. In Bama pigs, the abundance of various metabolites such as creatine, citric acid, L-valine and hypoxanthine is significantly higher than in Debao pigs, while the abundance of other metabolites, such as carnosine, is significantly lower. Among these, we propose six differential metabolites: L-proline, citric acid, ribose 1-phosphate, L-valine, creatine, and L-arginine, as well as four potential differential metabolites (without the KEGG pathway), alanyl-histidine, inosine 2'-phosphate, oleoylcarnitine, and histidinyl hydroxyproline, as features for evaluating the meat quality of Bama pigs and for differentiating pork from Bama pigs and Debao pigs. This study provides a proof-of-concept example of distinguishing pork from different pig breeds at the metabolite level and sheds light on elucidating the biological processes underlying meat quality differences. Our pork metabolites data are also of great value to the genomics breeding community in meat quality improvement.

Dynamic changes of acquired maternal SARS-CoV-2 IgG in infants.

At present, there are still ambiguous reports about the perinatal infection of infants born to mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dynamic characteristics of infantile serum antibodies born to mother with SARS-CoV-2 has not been well described. In this study, we analyzed the seroconversion of 27 newborns born to 26 pregnant women infected with SARS-CoV-2. The SARS-CoV-2 IgG positive rate of parturient was 80.8%, and half of their infants obtained maternal IgG. IgG transfer rates were 18.8% and 81.8% in those infants whose mother infected less and more than 2 weeks before delivery. In the first two months of life, the IgG level of infants dropped sharply to one tenth of that at birth. These results suggest that maternal SARS-CoV-2 IgG provides limited protection for infants.

Promoting effects of IL-13 on Ca2+ release and store-operated Ca2+ entry in airway smooth muscle cells.

Th2 cytokine interleukin (IL)-13 plays a central role in the pathogenesis of allergic asthma. IL-13 exhibits a direct effect on airway smooth muscle cells (ASMCs) to cause airway hyperresponsiveness. IL-13 has been demonstrated to regulate Ca(2+) signaling in ASMCs, but the underlying mechanisms are not fully understood. Store-operated Ca(2+) entry (SOCE) plays an important role in regulating Ca(2+) signaling and cellular responses of ASMCs, whether IL-13 affects SOCE in ASMCs has not been reported. In this study, by using confocal Ca(2+) fluorescence imaging, we found that IL-13 (10 ng/ml) treatment increased basal intracellular Ca(2+) ([Ca(2+)](i)) level, Ca(2+) release and SOCE induced by SERCA inhibitor thapsigargin in rat bronchial smooth muscle cells. The glucocorticoid dexamethasone and the short-acting beta2 adrenergic agonist (beta2 agonist) salbutamol suppressed IL-13-augumented basal [Ca(2+)](i), Ca(2+) release and SOCE, whereas the long-acting beta2 agonist salmeterol had no effect on altered Ca(2+) signaling in IL-13-treated ASMCs. Membrane-permeable cAMP analog dibutyryl-cAMP (db-cAMP) similarly decreased Ca(2+) release and SOCE induced by thapsigargin in IL-13-treated ASMCs, confirmed a role of cAMP/PKA signaling pathway in the regulation of SOCE. IL-13 promoted the proliferation of ASMCs stimulated by serum; this effect was inhibited by nonspecific Ca(2+) channel blockers SKF-96365 and NiCl(2), by salmeterol, but not by salbutamol and dexamethasone. IL-13 treatment did not change the expression of SOC channel-associated molecules STIM1, Orai1 and TRPC1 at mRNA level. Our findings identified a promoting effect of IL-13 on Ca(2+) release and SOCE in ASMCs, which partially contributes to its effect on the proliferation of ASMCs; the differences of glucocorticoids and beta2 agonists in inhibiting Ca(2+) signal and proliferation potentiated by IL-13 suggest that these therapies of asthma may have distinct effect on the relief of airway contraction and remodeling in bronchial asthma.

New Insights of Human Parvovirus B19 in Modulating Erythroid Progenitor Cell Differentiation.

Human parvovirus B19 (B19), a human pathogen of the erythroparvovirus genus, is responsible for a variety of diseases. B19 cause less symptoms in healthy individuals, also cause acute and chronic anemia in immunodeficiency patients. Transient aplastic crisis and pure red cell aplasia are two kinds of anemic hemogram, respectively, in acute and chronic B19 infection phase, especially occurring in patients with a shortened red cell survival or with immunodeficiency. In addition, B19-infected pregnant women may cause hydrops fetalis or fetal loss. B19 possesses high affinity to bone marrow and fetal liver due to its extremely restricted cytotoxicity to erythroid progenitor cells (EPCs) mediated by viral proteins. The nonstructural protein NS1 is considered to be the major pathogenic factor, which has been shown to inhibit the differentiation and maturation of EPCs through inducing viral DNA damage responses and cell cycle arrest. The time phase property of NS1 activity during DNA replication and conformity to transient change of hemogram are suggestive of its role in regulating differentiation of hematopoietic cells, which is not completely understood. In this review, we summarized the bridge between B19 NS1 and Notch signaling pathway or transcriptional factors GATA, which play an important role in erythroid cell proliferation and differentiation, to provide a new insight of the potential mechanism of B19-induced differential inhibition of EPCs.

Clinical characteristics and risk assessment of newborns born to mothers with COVID-19.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing an outbreak of pneumonia in Wuhan, Hubei Province, China, and other international areas. OBJECTIVE: Here, we report the clinical characteristics of the newborns delivered by SARS-CoV-2 infected pregnant women. METHODS: We prospectively collected and analyzed the clinical features, laboratory data and outcomes of 7 newborns delivered by SARS-CoV-2 infected pregnant women in Zhongnan Hospital of Wuhan University during January 20 to January 29, 2020. RESULTS: 4 of the 7 newborns were late preterm with gestational age between 36 weeks and 37 weeks, and the other 3 were full-term infants. The average birth weight was 2096 ± 660 g. All newborns were born without asphyxia. 2 premature infants performed mild grunting after birth, but relieved rapidly with non-invasive continuous positive airway pressure (nCPAP) ventilation. 3 cases had chest X-ray, 1 was normal and 2 who were supported by nCPAP presented mild neonatal respiratory distress syndrome (NRDS). Samples of pharyngeal swab in 6 cases, amniotic fluid and umbilical cord blood in 4 cases were tested by qRT-PCR, and there was no positive result of SARS-CoV-2 nucleic acid in all cases. CONCLUSIONS: The current data show that the infection of SARS-CoV-2 in late pregnant women does not cause adverse outcomes in their newborns, however, it is necessary to separate newborns from mothers immediately to avoid the potential threats.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer.

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan-Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

Phototherapy is associated with the decrease in serum globulin levels in neonatal hyperbilirubinemia.

Previous studies have indicated that phototherapy may be associated with childhood immune disorders in later life. The present study aimed to assess the effects of phototherapy as a risk factor in the decrease in serum globulin (GLB) levels during neonatal hyperbilirubinemia. A total of 430 full-term infants aged between 1 and 28 days, diagnosed with neonatal hyperbilirubinemia, were enrolled in the present study. Neonates with intrauterine infection, genetic abnormalities and congenital diseases were excluded from the cohort. All neonates received single-side phototherapy (halogen lamps for 12 h per day, for 3 days) and/or intravenous albumin (IVALB; 1 g/kg/day, for 2 days) and/or intravenous immunoglobulin (1 g/kg/day, for 2 days). Total serum bilirubin (TSB), albumin (ALB) and GLB levels were examined twice, on the first and fourth days of hospitalization. Neonatal TSB concentrations decreased from 299.6±83.9 to 163.6±57.6 µmol/l following 3 days of intensive treatment (P<0.001). Pearson correlative analysis indicated that TSB was significantly correlated to the GLB level (r=0.249; P<0.01), but not with ALB level. There was a significant decrease in GLB levels following phototherapy+IVALB (P<0.001). The GLB levels decreased to 2-4 g/l (10-20% compared with their baseline levels) and were markedly decreased in infants >16 days old compared with those in patients aged <16 days (P<0.001). The decreases in GLB levels observed were 21.3±4.1 to 18.5±4.2 g/l in the phototherapy group, and 23.0±3.9 to 16.6±4.5 g/l in the phototherapy+IVALB (P<0.001). The decrease in GLB levels was associated with age (95% confidence interval; -0.152, -0.016). The results demonstrated that phototherapy decreased serum GLB levels, particularly in infants aged >16 days, while additional IVALB treatment promoted the decrease, along with increased age.